By Michael Smith, North American Correspondent, MedPage Today
Published: June 21, 2013
- New approaches to HIV testing can detect acute infections that would have gone undetected with older methods.
- Note that new 4th-generation tests detect both immunoglobulin M-class and G-class antibodies as well as the p24 antigen whereas early immunoassays detected only immunoglobulin G-class antibodies to HIV.
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
New approaches to HIV testing can detect acute infections that would have gone undetected with older methods, according to a CDC report.
A 4th-generation immunoassay, coupled with an HIV-1/HIV-2 antibody differentiation test, picked up acute infections where traditional methods did not, according to two studies reported by CDC in the June 20 issue of Morbidity and Mortality Weekly Report.
The acute phase of infection -- which plays a "disproportionate" role in transmission -- is the period between the appearance of HIV RNA in plasma and the detection of HIV antibodies, the agency noted.
Testing for HIV has usually begun with an immunoassay, followed by a Western blot or indirect immunofluorescence assay if the initial test is positive.
Early immunoassays detected only immunoglobulin G-class antibodies to HIV. That was improved so that 4th-generation tests detect both immunoglobulin M-class and G-class antibodies as well as the p24 antigen, an important HIV protein.
Because the p24 antigen can be detected before antibodies appear, the 4th-generation tests can pick up some acute HIV infections, the agency report noted.
But a negative supplemental test with a Western blot or indirect immunofluorescence assay has often resulted in erroneously classifying people as HIV-negative, the report added.
Two evaluations of the new test algorithm suggest it is likely to do better:
- HIV screening at a Phoenix emergency department identified 37 undiagnosed HIV infections from July 2011 through February 2013, including 12 (or 32.4%) in the acute phase that would not have been found using earlier methods.
- A three-site screening program found 99 cases with a positive first test and a negative supplemental test; 55 (or 55.6%) were shown to be acute HIV infections but a large proportion of those would not have been found by traditional methods.
The new algorithm begins with a 4th-generation immunoassay, followed by the HIV-1/HIV-2 antibody test. If that second assay is negative or indeterminate, the definitive step is testing for the presence of HIV RNA.
In the Phoenix emergency room, the agency reported, the first test found 37 cases of infection, including 25 in which the supplemental test was positive and 12 in which it was negative or indeterminate.
RNA testing confirmed acute HIV infection in those 12, the CDC report said.
The median HIV viral load among those 12 was 3,636,176 copies of HIV RNA per milliliter, compared with 27,125 copies per milliliter among the 25 with established infection, the report said.
In the Screening Targeted Populations to Interrupt On-going Chains of HIV Transmission with Enhanced Partner Notification (STOP) study, initial testing of 37,876 patients, screened from September 2011 through September 2012, found HIV in 654, or 1.7%.
Of those, 99 had a negative or indeterminate result on the HIV-1/HIV-2 antibody differentiation test, but HIV RNA was present in 55, indicating an acute infection. The traditional supplemental tests -- Western blot or indirect immunofluorescence assay -- were negative in 37 cases and indeterminate in seven, the agency reported.
Taken together, the agency report said, the findings show that acute HIV infection detected with newer immunoassays is often misclassified as HIV-negative by traditional supplemental tests, "potentially leading to adverse clinical outcomes for patients and further HIV transmission within the community."
The researchers cautioned that the findings might not apply to all screening programs. The Phoenix program aimed to screen as many people as possible, but some tests might have been ordered because of an increased index of suspicion.
And the STOP study looked at people at high risk for HIV, so that the proportion of infections that were acute might be higher than in other populations, the agency report noted.
The analysis was supported by the CDC. Peters is an employee of the agency.
Primary source: Morbidity and Mortality Weekly Report
Centers for Disease Control and Prevention "Detection of acute HIV infection in two evaluations of a new HIV diagnostic testing algorithm -- United States, 2011–2013" MMWR 2013; 62: 489-494.